CHAPTER CONTENTS
PICORNAVIRUSES
Enteroviruses
Rhinoviruses
CALICIVIRUSES
Norovirus
REOVIRUSES
Rotavirus
Self-Assessment Questions
Summaries of Organisms
Practice Questions: USMLE & Course Examinations
PICORNAVIRUSES
Picornaviruses are small (20–30 nm) nonenveloped viruses composed of an icosahedral nucleocapsid and a single-stranded RNA genome. The genome RNA has positive polarity (i.e., on entering the cell, it functions as the viral mRNA). There is no polymerase within the virion. Picornaviruses replicate in the cytoplasm of cells. They are not inactivated by lipid solvents, such as ether, because they do not have an envelope.
The picornavirus family includes two groups of medical importance: the enteroviruses and the rhinoviruses. Among the major enteroviruses are poliovirus, Coxsackie viruses, echoviruses, and hepatitis A virus (which is described in Chapter 41). Enteroviruses infect primarily the enteric tract, whereas rhinoviruses are found in the nose and throat (rhino = nose) (Table 40–1).
TABLE 40–1 Picornaviruses of Medical Importance
Enteroviruses replicate optimally at 37°C, whereas rhinoviruses grow better at 33°C, in accordance with the lower temperature of the nose. Enteroviruses are stable under acid conditions (pH 3–5), which enables them to survive exposure to gastric acid, whereas rhinoviruses are acid-labile. This explains why rhinovirus infections are restricted to the nose and throat.
Important features of viruses that commonly infect the intestinal tract are summarized in Table 40–2. These include the picornaviruses but also rotavirus and norovirus, which are described later in this chapter, and adenovirus, which is described in Chapter 38.
TABLE 40–2 Features of Viruses Commonly Infecting the Intestinal Tract
ENTEROVIRUSES
1. Poliovirus
Disease
This virus causes poliomyelitis.
Important Properties
The host range is limited to primates (i.e., humans and non-human primates such as apes and monkeys). This limitation is due to the binding of the viral capsid protein to a receptor found only on primate cell membranes. However, note that purified viral RNA (without the capsid protein) can enter and replicate in many nonprimate cells—the RNA can bypass the cell membrane receptor (i.e., it is “infectious RNA”).
There are three serologic (antigenic) types based on different antigenic determinants on the outer capsid proteins. Because there is little cross-reaction, protection from disease requires the presence of antibody against each of the three types.
Summary of Replicative Cycle
The virion interacts with specific cell receptors on the cell membrane and then enters the cell. The capsid proteins are then removed. After uncoating, the genome RNA functions as mRNA and is translated into one very large polypeptide called noncapsid viral protein 00. This polypeptide is cleaved by a virus-encoded protease in multiple steps to form both the capsid proteins of the progeny virions and several noncapsid proteins, including the RNA polymerase that synthesizes the progeny RNA genomes. Replication of the genome occurs by synthesis of a complementary negative strand, which then serves as the template for the positive strands. Some of these positive strands function as mRNA to make more viral proteins, and the remainder become progeny virion genome RNA. Assembly of the progeny virions occurs by coating of the genome RNA with capsid proteins. Virions accumulate in the cell cytoplasm and are released upon death of the cell. They do not bud from the cell membrane.
Transmission & Epidemiology
Poliovirus is transmitted by the fecal–oral route. It replicates in the oropharynx and intestinal tract. Humans are the only natural hosts.
As a result of the success of the vaccine, poliomyelitis caused by naturally occurring “wild-type” virus has been eradicated from the United States and, indeed, from the entire Western hemisphere. The rare cases in the United States occur mainly in (1) people exposed to virulent revertants of the attenuated virus in the live vaccine and (2) unimmunized people exposed to wild-type poliovirus while traveling abroad. Before the vaccine was available, epidemics occurred in the summer and fall.
The World Health Organization set the eradication of paralytic polio by 2005 as a goal. Unfortunately, this goal was not achieved. In 1988, there were 388,000 cases of paralytic polio worldwide, whereas in 2005 there were fewer than 2000. Despite this remarkable decrease, paralytic polio continues to occur. As of 2012, there was still a total of approximately 200 cases each year in three countries: Afghanistan, Nigeria, and Pakistan. Thus far, smallpox is the only infectious disease that has been eradicated, a consequence of the worldwide use of the smallpox vaccine.
Pathogenesis & Immunity
After replicating in the oropharynx and small intestine, especially in lymphoid tissue, the virus spreads through the bloodstream to the central nervous system. It can also spread retrograde along nerve axons.
In the central nervous system, poliovirus preferentially replicates in the motor neurons located in the anterior horn of the spinal cord. Death of these cells results in paralysis of the muscles innervated by those neurons. Paralysis is not due to virus infection of muscle cells. The virus also affects the brainstem, leading to “bulbar” poliomyelitis (with respiratory paralysis), but rarely damages the cerebral cortex.
In infected individuals, the immune response consists of both intestinal IgA and humoral IgG to the specific sero-type. Infection provides lifelong type-specific immunity.
Clinical Findings
The range of responses to poliovirus infection includes (1) inapparent, asymptomatic infection; (2) abortive poliomyelitis; (3) nonparalytic poliomyelitis; and (4) paralytic poliomyelitis. Asymptomatic infection is quite common. Roughly 1% of infections are clinically apparent. The incubation period is usually 10 to 14 days.
The most common clinical form is abortive poliomyelitis, which is a mild, febrile illness characterized by headache, sore throat, nausea, and vomiting. Most patients recover spontaneously. Nonparalytic poliomyelitis manifests as aseptic meningitis with fever, headache, and a stiff neck. This also usually resolves spontaneously. In paralytic poliomyelitis, flaccid paralysis is the predominant finding, but brainstem involvement can lead to life-threatening respiratory paralysis. Painful muscle spasms also occur. The motor nerve damage is permanent, but some recovery of muscle function occurs as other nerve cells take over. In paralytic polio, both the meninges and the brain parenchyma (meningoencephalitis) are often involved. If the spinal cord is also involved, the term meningomyeloencephalitis is often used.
A postpolio syndrome that occurs many years after the acute illness has been described. Marked deterioration of the residual function of the affected muscles occurs many years after the acute phase. The cause of this deterioration is unknown.
No permanent carrier state occurs following infection by poliovirus, but virus excretion in the feces can occur for several months.
Laboratory Diagnosis
The diagnosis is made either by isolation of the virus or by a rise in antibody titer. Virus can be recovered from the throat, stool, or spinal fluid by inoculation of cell cultures. The virus causes a cytopathic effect (CPE) and can be identified by neutralization of the CPE with specific antisera.
Treatment
There is no antiviral therapy. Treatment is limited to symptomatic relief and respiratory support, if needed. Physiotherapy for the affected muscles is important.
Prevention
Poliomyelitis can be prevented by both the killed vaccine (Salk vaccine, inactivated vaccine, IPV) and the live, attenuated vaccine (Sabin vaccine, oral vaccine, OPV) (Table 40–3). Both vaccines induce humoral antibodies, which neutralize virus entering the blood and hence prevent central nervous system infection and disease. Both the killed and the live vaccines contain all three serotypes. At present, the inactivated vaccine is preferred for reasons that are described later.
TABLE 40–3 Important Features of Poliovirus Vaccines
The current version of the inactivated vaccine is called enhanced polio vaccine, or eIPV. It has a higher seroconversion rate and induces a higher titer of antibody than the previous IPV. eIPV also induces some mucosal immunity IgA, making it capable of interrupting transmission, but the amount of secretory IgA induced by eIPV is significantly less than the amount induced by OPV. OPV is therefore preferred for eradication efforts. The only version of polio vaccine currently produced in the United States is eIPV. In certain countries where polio remains endemic (e.g., India), a monovalent oral polio vaccine is used because the rate of seroconversion is higher with the monovalent vaccine than with the trivalent one.
In the past, the live vaccine was preferred in the United States for two main reasons: (1) It interrupts fecal–oral transmission by inducing secretory IgA in the gastrointestinal tract. (2) It is given orally and so is more readily accepted than the killed vaccine, which must be injected.
The live vaccine has four disadvantages: (1) Rarely, reversion of the attenuated virus to virulence will occur, and disease may ensue (especially for the type 3 virus). (2) It can cause disease in immunodeficient persons and therefore should not be given to them. (3) Infection of the gastrointestinal tract by other enteroviruses can limit replication of the vaccine virus and reduce protection. (4) It must be kept refrigerated to prevent heat inactivation of the live virus.
Outbreaks of paralytic polio caused by vaccine-derived poliovirus (VDPV) continue to occur, especially in areas where there are large numbers of unimmunized people. These VDPV strains have lost their attenuation by acquiring genes from wild-type enteroviruses by recombination. Outbreaks of VDPV-associated paralytic polio have been contained by campaigns to immunize people in the affected area with the oral (Sabin) vaccine that interrupts fecal–oral transmission.
The duration of immunity is thought to be longer with the live than with the killed vaccine, but a booster dose is recommended with both.
The currently approved vaccine schedule consists of four doses of inactivated vaccine administered at 2 months, 4 months, 6 to 18 months, and upon entry to school at 4 to 6 years. One booster (lifetime) is recommended for adults who travel to endemic areas. The use of the inactivated vaccine should prevent some of the approximately 10 cases per year of vaccine-associated paralytic polio that arise from reversion of the attenuated virus in the vaccine.
In the past, some lots of poliovirus vaccines were contaminated with a papovavirus, SV40 virus, which causes sarcomas in rodents. SV40 virus was a “passenger” virus in the monkey kidney cells used to grow the poliovirus for the vaccine. Fortunately, no increase in cancer occurred in persons inoculated with the SV40 virus–containing polio vaccine. However, there is some evidence that SV40 DNA can be found in certain human cancers such as non-Hodgkin’s lymphoma; the role of SV40 as a cause of cancer in persons immunized with early versions of the polio vaccine is unresolved. At present, cell cultures used for vaccine purposes are carefully screened to exclude the presence of adventitious viruses.
Passive immunization with immune serum globulin is available for protection of unimmunized individuals known to have been exposed. Passive immunization of newborns as a result of passage of maternal IgG antibodies across the placenta also occurs.
Quarantine of patients with disease is not effective, because fecal excretion of the virus occurs in infected individuals prior to the onset of symptoms and in those who remain asymptomatic.
2. Coxsackie Viruses
Coxsackie viruses are named for the town of Coxsackie, NY, where they were first isolated.
Diseases
Coxsackie viruses cause a variety of diseases. Group A viruses cause, for example, herpangina, acute hemorrhagic conjunctivitis, and hand-foot-and-mouth disease, whereas group B viruses cause pleurodynia, myocarditis, and pericarditis. Both types cause nonspecific upper respiratory tract disease (common cold), febrile rashes, and aseptic meningitis. Coxsackie viruses and echoviruses (see next section) together cause approximately 90% of cases of viral (aseptic) meningitis.
Important Properties
The size and structure of the virion and the nature of the genome RNA are similar to those of poliovirus. The classification of Coxsackie viruses into group A or B is based on pathogenicity in mice. Group A viruses cause widespread myositis and flaccid paralysis, which is rapidly fatal, whereas group B viruses cause generalized, less severe lesions of the heart, pancreas, and central nervous system and focal myositis. At least 24 serotypes of Coxsackie virus A and 6 serotypes of Coxsackie virus B are recognized.
Summary of Replicative Cycle
Replication is similar to that of poliovirus.
Transmission & Epidemiology
Coxsackie viruses are transmitted primarily by the fecal–oral route, but respiratory aerosols also play a role. They replicate in the oropharynx and the intestinal tract. Humans are the only natural hosts. Coxsackie virus infections occur worldwide, primarily in the summer and fall.
Pathogenesis & Immunity
Group A viruses have a predilection for skin and mucous membranes, whereas group B viruses cause disease in various organs such as the heart, pleura, pancreas, and liver. Both group A and B viruses can affect the meninges and the motor neurons (anterior horn cells) to cause paralysis. From their original site of replication in the oropharynx and gastrointestinal tract, they disseminate via the bloodstream.
Immunity following infection is provided by type-specific IgG antibody.
Clinical Findings
Group A–Specific Diseases
Herpangina is characterized by fever, sore throat, and tender vesicles in the oropharynx. Hand-foot-and-mouth disease is characterized by a vesicular rash on the hands and feet and ulcerations in the mouth, mainly in children.
Group B–Specific Diseases
Pleurodynia (Bornholm disease, epidemic myalgia, “devil’s grip”) is characterized by fever and severe pleuritic-type chest pain. Note that pleurodynia is pain due to an infection of the intercostal muscles (myositis), not of the pleura.
Myocarditis and pericarditis are characterized by fever, chest pain, and signs of congestive failure. Dilated cardiomyopathy with global hypokinesia of the myocardium is a feared sequela that often requires cardiac transplantation to sustain life. Diabetes in mice can be caused by pancreatic damage as a result of infection with Coxsackie virus B4. This virus is suspected to have a similar role in juvenile diabetes in humans.
Diseases Caused by Both Groups
Both groups of viruses can cause aseptic meningitis, mild paresis, and acute flaccid paralysis similar to poliomyelitis. Upper respiratory infections, pharyngitis, and minor febrile illnesses with or without rash can occur also.
Laboratory Diagnosis
The diagnosis is made either by isolating the virus in cell culture or suckling mice or by observing a rise in titer of neutralizing antibodies. A rapid (2.5-hour) polymerase chain reaction (PCR)–based test for enteroviral RNA in the spinal fluid is useful for making a prompt diagnosis of viral meningitis because culture techniques typically take days to obtain a result.
Treatment & Prevention
There is neither antiviral drug therapy nor a vaccine available against these viruses. No passive immunization is recommended.
3. Echoviruses
The prefix ECHO is an acronym for enteric cytopathic human orphan. Although called “orphans” because they were not initially associated with any disease, they are now known to cause a variety of diseases such as aseptic meningitis, upper respiratory tract infection, febrile illness with and without rash, infantile diarrhea, and hemorrhagic conjunctivitis.
The structure of echoviruses is similar to that of other enteroviruses. More than 30 serotypes have been isolated. In contrast to Coxsackie viruses, they are not pathogenic for mice. Unlike polioviruses, they do not cause disease in monkeys. They are transmitted by the fecal–oral route and occur worldwide. Pathogenesis is similar to that of the other enteroviruses.
Along with Coxsackie viruses, echoviruses are one of the leading causes of aseptic (viral) meningitis. The diagnosis is made by isolation of the virus in cell culture. Serologic tests are of little value, because there are a large number of serotypes and no common antigen. There is no antiviral therapy or vaccine available.
4. Other Enteroviruses
In view of the difficulty in classifying many enteroviruses, all new isolates have been given a simple numerical designation since 1969.
Enterovirus 70 is the main cause of acute hemorrhagic conjunctivitis, characterized by petechial hemorrhages on the bulbar conjunctivas. Complete recovery usually occurs, and there is no therapy.
Enterovirus 71 is one of the leading causes of viral central nervous system disease, including meningitis, encephalitis, and paralysis. It also causes diarrhea, pulmonary hemorrhages, hand-foot-and-mouth disease, and herpangina. Enterovirus 72 is hepatitis A virus, which is described in Chapter 41.
RHINOVIRUSES
Disease
These viruses are the main cause of the common cold.
Important Properties
There are more than 100 serologic types, which explains why the common cold is so common. As described in Table 40–1, they replicate better at 33°C than at 37°C, which explains why they affect primarily the nose and conjunctiva rather than the lower respiratory tract. Because they are acid-labile, they are killed by gastric acid when swallowed. This explains why they do not infect the gastrointestinal tract, unlike the enteroviruses. The host range is limited to humans and chimpanzees.
Summary of Replicative Cycle
Replication is similar to that of poliovirus. The cell surface receptor for rhinoviruses is intracellular adhesion molecule 1 (ICAM-1), an adhesion protein located on the surface of many types of cells.
Transmission & Epidemiology
There are two modes of transmission for these viruses. In the past, it was accepted that they were transmitted directly from person to person via aerosols of respiratory droplets. However, now it appears that an indirect mode, in which respiratory droplets are deposited on the hands or on a surface such as a table and then transported by fingers to the nose or eyes, is also important.
The common cold is reputed to be the most common human infection, although data are difficult to obtain because it is not a well-defined or notifiable disease. Millions of days of work and school are lost each year as a result of “colds.” Rhinoviruses occur worldwide, causing disease particularly in the fall and winter. The reason for this seasonal variation is unclear. Low temperatures per se do not predispose to the common cold, but the crowding that occurs at schools, for example, may enhance transmission during fall and winter. The frequency of colds is high in childhood and tapers off during adulthood, presumably because of the acquisition of immunity.
A few serotypes of rhinoviruses are prevalent during one season, only to be replaced by other serotypes during the following season. It appears that the population builds up immunity to the prevalent serotypes but remains susceptible to the others.
Pathogenesis & Immunity
The portal of entry is the upper respiratory tract, and the infection is limited to that region. Rhinoviruses rarely cause lower respiratory tract disease, probably because they grow poorly at 37°C.
Immunity is serotype-specific and is a function of nasal secretory IgA rather than humoral antibody.
Clinical Findings
After an incubation period of 2 to 4 days, sneezing, nasal discharge, sore throat, cough, and headache are common. A chilly sensation may occur, but there are few other systemic symptoms. The illness lasts about 1 week. Note that other viruses such as coronaviruses, adenoviruses, influenza C virus, and Coxsackie viruses also cause the common cold syndrome.
Laboratory Diagnosis
Diagnosis can be made by isolation of the virus from nasal secretions in cell culture, but this is rarely attempted. Serologic tests are not done.
Treatment & Prevention
No specific antiviral therapy is available. Vaccines appear impractical because of the large number of serotypes. Paper tissues impregnated with a combination of citric acid (which inactivates rhinoviruses) and sodium lauryl sulfate (a detergent that inactivates enveloped viruses such as influenza virus and respiratory syncytial virus) limit transmission when used to remove viruses from fingers contaminated with respiratory secretions. High doses of vitamin C have little ability to prevent rhinovirus-induced colds. Lozenges containing zinc gluconate are available for the treatment of the common cold, but their efficacy remains uncertain.
CALICIVIRUSES
Caliciviruses are small, nonenveloped viruses with single-stranded RNA of positive polarity. Although they share those features with picornaviruses, caliciviruses are distinguished from picornaviruses by having a larger genome and having distinctive spikes on the surface. Norovirus is the main human pathogen in the calicivirus family.
NOROVIRUS
Disease
Norovirus is one of the most common causes of viral gastroenteritis in adults both in the United States and worldwide. Norovirus is also the most common cause of viral gastroenteritis in children in the United States because the rotavirus vaccine has lowered the incidence of disease caused by that virus. Norwalk virus is an important norovirus and is named for an outbreak of gastroenteritis in a school in Norwalk, OH, in 1969.
Important Properties
Norovirus has a nonsegmented, single-stranded, positive-polarity RNA genome. It is a nonenveloped virus with an icosahedral nucleocapsid. There is no polymerase within the virion. In the electron microscope, 10 prominent spikes and 32 cup-shaped depressions can be seen. There are many serotypes; the exact number is uncertain. Five genogroups have been identified. Most human infections are caused by members of genogroup II.
Summary of Replicative Cycle
Norovirus replicates in a manner similar to that of poliovirus (see earlier in this chapter).
Transmission & Epidemiology
Norovirus is transmitted by the fecal–oral route, often involving the ingestion of contaminated seafood or water. Outbreaks typically occur in group settings such as cruise ships (especially in the Caribbean region), schools, camps, hospitals, and nursing homes. Person-to-person transmission also occurs, especially in group settings. There are many animal caliciviruses, but there is no evidence that they cause human infection.
Infection is enhanced by several features of the virus: low infectious dose, excretion of virus in the stool both before the onset of symptoms and for several weeks after recovery, and resistance to inactivation by chlorination and to drying in the environment. It is thought to remain infectious for several days in water, uncooked food, and on environmental surfaces such as door handles.
Pathogenesis & Immunity
Norovirus infection is typically limited to the mucosal cells of the intestinal tract. Watery diarrhea without red cells or white cells occurs. Many asymptomatic infections occur, as determined by the detection of antibodies. Immunity following infection appears to be brief, and reinfection can occur. New strains appear every 2 to 4 years and cause widespread infections.
Clinical Findings
Disease is characterized by sudden onset of vomiting and diarrhea accompanied by low-grade fever and abdominal cramping. Neither the emesis nor the stool contains blood. The illness typically lasts 2 to 3 days, and there are no long-term sequelae, except in some immunocompromised patients in whom chronic gastroenteritis can occur. In some outbreaks, certain patients manifest signs of central nervous system involvement such as headache, meningismus, photophobia, and obtundation.
Laboratory Diagnosis
A PCR-based test on the stool is performed when a specific diagnosis is required. However, the diagnosis is often a clinical one.
Treatment & Prevention
There is no antiviral therapy or vaccine available. Dehydration and electrolyte imbalance caused by the vomiting and diarrhea may require oral rehydration or intravenous fluids. Personal hygiene, such as handwashing, and public health measures, such as proper sewage disposal and disinfection of contaminated surfaces, are helpful.
REOVIRUSES
REO is an acronym for respiratory enteric orphan; when the virus was discovered, it was isolated from the respiratory and enteric tracts and was not associated with any disease. Rotaviruses are the most important human pathogens in the reovirus family.
ROTAVIRUS
Disease
Rotavirus is a common cause of viral gastroenteritis, especially in young children.
Important Properties
Rotavirus has a segmented, double-stranded RNA genome surrounded by a double-layered icosahedral capsid without an envelope. The rotavirus genome has 11 segments. The virion contains an RNA-dependent RNA polymerase. A virion polymerase is required because human cells do not have an RNA polymerase that can synthesize mRNA from a double-stranded RNA template.
Many domestic animals are infected with their own strains of rotaviruses, but these are not a source of human disease. There are at least six serotypes of human rotavirus. The outer surface protein (also known as the viral hemagglutinin) is the type-specific antigen and elicits protective antibody.
Summary of Replicative Cycle
Rotavirus attaches to the cell surface at the site of the β-adrenergic receptor. After entry of the virion into the cell, the RNA-dependent RNA polymerase synthesizes mRNA from each of the 11 segments within the cytoplasm. The 11 mRNAs are translated into the corresponding number of structural and nonstructural proteins. One of these, an RNA polymerase, synthesizes minus strands that will become part of the genome of the progeny virus. Capsid proteins form an incomplete capsid around the minus strands, and then the plus strands of the progeny genome segments are synthesized. The virus is released from the cytoplasm by lysis of the cell, not by budding.
Transmission & Epidemiology
Rotavirus is transmitted by the fecal–oral route. Infection occurs worldwide, and by age 6 years, most children have antibodies to at least one serotype.
Pathogenesis & Immunity
Rotavirus replicates in the mucosal cells of the small intestine, resulting in the excess secretion of fluids and electrolytes into the bowel lumen. The consequent loss of salt, glucose, and water leads to diarrhea. No inflammation occurs, and the diarrhea is nonbloody. It is thought that this watery diarrhea is caused primarily by stimulation of the enteric nervous system.
The virulence of certain reoviruses in mice has been localized to the proteins encoded by several specific genome segments. For example, one gene governs tissue tropism, whereas another controls the inhibition of cell RNA and protein synthesis.
Immunity to rotavirus infection is unclear. It is likely that intestinal IgA directed against specific serotypes protects against reinfection and that colostrum IgA protects newborns up to the age of 6 months.
Clinical Findings
Rotavirus infection is characterized by nausea, vomiting, and watery, nonbloody diarrhea. Gastroenteritis is most serious in young children, in whom dehydration and electrolyte imbalance are a major concern. Adults usually have minor symptoms.
Laboratory Diagnosis
Although the diagnosis of most cases of viral gastroenteritis does not involve the laboratory, a diagnosis can be made by detection of rotavirus in the stool by using radioimmunoassay or enzyme-linked immunosorbent assay (ELISA). This approach is feasible because there are large numbers of virus particles in the stool. The original demonstration of rotavirus in the stool was done by immunoelectron microscopy, in which antibody aggregated the virions, allowing them to be visualized in the electron microscope. This technique is not feasible for routine clinical use. In addition to antigen detection, the diagnosis can be made by observation of a fourfold or greater rise in antibody titer. Although the virus can be cultured, this procedure is not routinely done.
Treatment & Prevention
There are two rotavirus vaccines available. Both contain live virus and are given orally. One is a live, attenuated vaccine (Rotarix), which contains the single most common rotavirus serotype (G1) causing disease in the United States. The other is a live reassortant vaccine (Rotateq), which contains five rotavirus strains. Patients with a history of intussusception should not receive either vaccine.
The five rotaviruses in the Rotateq vaccine are reassortants in which the gene for the outer surface protein of a human rotavirus is inserted into a bovine strain of rotavirus. (Recall that rotavirus has a segmented genome.) The bovine strain is nonpathogenic for humans, but the human outer surface protein in the vaccine virus elicits protective (IgA) immunity in the gastrointestinal tract.
A previously approved vaccine (Rotashield) was withdrawn when a high rate of intussusception occurred in vaccine recipients. Hygienic measures such as proper sewage disposal and handwashing are helpful. There is no antiviral therapy.
SELF-ASSESSMENT QUESTIONS
1. Regarding poliovirus and the disease poliomyelitis, which one of the following is most accurate?
(A) Poliovirus is transmitted primarily by the fecal–oral route.
(B) New antigenic variants arise by coinfection with animal strains of poliovirus.
(C) Paralytic poliomyelitis is the most common manifestation of poliovirus infection.
(D) Poliovirus has single-stranded RNA as its genome and a polymerase in the virion that synthesizes its mRNA.
(E) The current vaccine recommendation is to give the live, attenuated vaccine for the first three immunizations to prevent the child from acting as a reservoir, followed by boosters using the killed vaccine.
2. A 70-year-old retired carpenter has signed up with a volunteer organization to build houses in a developing country where polio is still endemic. He plans to be there about 9 months. He thinks he has never been immunized against polio. Which one of the following is the most appropriate thing to do?
(A) Give immune serum globulins (ISG).
(B) Give the killed vaccine containing only type 3.
(C) Give the killed vaccine containing types 1, 2, and 3.
(D) Give the live vaccine containing only type 3.
(E) Give the live vaccine containing types 1, 2, and 3.
3. Regarding rhinoviruses, which one of the following is most accurate?
(A) Rhinoviruses are an important cause of viral meningitis and myocarditis.
(B) The rhinovirus vaccine is recommended for all children over 2 years of age.
(C) Rhinoviruses have many serologic types, so a person can have many infections caused by these viruses.
(D) Rhinoviruses are not inactivated by stomach acid, so they infect the upper gastrointestinal tract and are one of the causes of viral diarrhea.
(E) An important feature of the laboratory diagnosis of rhinoviruses is finding cytopathic effect in cell culture consisting of multinucleated giant cells.
4. Regarding norovirus, which one of the following is most accurate?
(A) The diarrhea is caused by an exotoxin that increases cyclic adenosine monophosphate (cyclicAMP).
(B) There are no neutrophils or red cells in the stool.
(C) Ritonavir, a protease inhibitor, is the drug of choice for chronic diarrhea caused by norovirus.
(D) Ingestion of undercooked hamburger is a common mode of acquisition of norovirus as cattle are a major reservoir of the virus.
(E) The diagnosis of norovirus-induced diarrhea is typically made by the detection of a fourfold or greater rise in antibody titer to the virus.
5. Regarding rotavirus, which one of the following is most accurate?
(A) Rotavirus is a major cause of nosocomial diarrhea in intensive care units.
(B) The vaccine against rotavirus contains live, attenuated virus as the immunogen.
(C) Rotavirus has a nonsegmented, single-stranded RNA genome, and there is no polymerase in the virion.
(D) The diagnosis of rotavirus diarrhea is typically made by the detection of a fourfold or greater rise in antibody titer to the virus.
(E) Diarrhea caused by rotavirus is due to a viral protein that increases the release of IgA from many submucosal B lymphocytes.
ANSWERS
1. (A)
2. (C)
3. (C)
4. (B)
5. (B)
SUMMARIES OF ORGANISMS
Brief summaries of the organisms described in this chapter begin on page 648. Please consult these summaries for a rapid review of the essential material.
PRACTICE QUESTIONS: USMLE & COURSE EXAMINATIONS
Questions on the topics discussed in this chapter can be found in the Clinical Virology section of PART XIII: USMLE (National Board) Practice Questions starting on page 703. Also see PART XIV: USMLE (National Board) Practice Examination starting on page 731.